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https://www.readbyqxmd.com/read/29147991/the-role-of-the-gut-microbiome-in-multiple-sclerosis-risk-and-progression-towards-characterization-of-the-ms-microbiome
#1
REVIEW
Anne-Katrin Pröbstel, Sergio E Baranzini
Multiple sclerosis (MS) is the prototypic complex disease, in which both genes and the environment contribute to its pathogenesis. To date, > 200 independent loci across the genome have been associated with MS risk. However, these only explain a fraction of the total phenotypic variance, suggesting the possible presence of additional genetic factors, and, most likely, also environmental factors. New DNA sequencing technologies have enabled the sequencing of all kinds of microorganisms, including those living in and around humans (i...
November 16, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29143589/biomarkers-in-the-evolution-of-multiple-sclerosis
#2
Thomas Berger
Nonimaging biomarkers can be applied in differential diagnosis, evaluation of disease progression and therapy monitoring of multiple sclerosis (MS). Presence of oligoclonal IgG bands in cerebrospinal fluid is a diagnostic element and a negative predictor of MS evolution. AQP4 antibodies are pathogenic and diagnostic for neuromyelitis optica spectrum disorder. Antibodies to myelin oligodendrocyte glycoprotein develop in about 50% of predominantly pediatric patients with acute disseminated encephalomyelitis, but their possible role in pathogenesis is unknown...
November 2017: Neurodegenerative Disease Management
https://www.readbyqxmd.com/read/29143550/safety-and-tolerability-of-inebilizumab-medi-551-an-anti-cd19-monoclonal-antibody-in-patients-with-relapsing-forms-of-multiple-sclerosis-results-from-a-phase-1-randomised-placebo-controlled-escalating-intravenous-and-subcutaneous-dose-study
#3
Mark A Agius, Gabriela Klodowska-Duda, Maciej Maciejowski, Andrzej Potemkowski, Jing Li, Kaushik Patra, Jacob Wesley, Soraya Madani, Gerard Barron, Eliezer Katz, Armando Flor
BACKGROUND: B cells may be involved in the pathophysiology of multiple sclerosis (MS). Inebilizumab (formerly MEDI-551) binds to and depletes CD19(+) B cells. OBJECTIVES: To assess safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of inebilizumab in adults with relapsing MS. METHODS: This phase 1 trial randomised 28 patients 3:1 (21, inebilizumab; 7, placebo) to inebilizumab (2 intravenous (IV) doses, days 1 and 15: 30, 100 or 600 mg; or single subcutaneous (SC) dose on day 1: 60 or 300 mg) or matching placebo, with follow-up until at least week 24 or return of CD19(+) B-cell count to ⩾80 cells/µL...
November 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29143287/lipoic-acid-stimulates-camp-production-in-healthy-control-and-secondary-progressive-ms-subjects
#4
Sarah E Fiedler, Vijayshree Yadav, Amelia R Kerns, Catherine Tsang, Sheila Markwardt, Edward Kim, Rebecca Spain, Dennis Bourdette, Sonemany Salinthone
Lipoic acid (LA) exhibits antioxidant and anti-inflammatory properties; supplementation reduces disease severity and T lymphocyte migration into the central nervous system in a murine model of multiple sclerosis (MS), and administration in secondary progressive MS (SPMS) subjects reduces brain atrophy compared to placebo. The mechanism of action (MOA) of LA's efficacy in suppression of MS pathology is incompletely understood. LA stimulates production of the immunomodulator cyclic AMP (cAMP) in vitro. To determine whether cAMP could be involved in the MOA of LA in vivo, we performed a clinical trial to examine whether LA stimulates cAMP production in healthy control and MS subjects, and whether there are differences in the bioavailability of LA between groups...
November 15, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29143164/upregulation-of-myelin-gene-expression-by-a-physically-modified-saline-via-phosphatidylinositol-3-kinase-mediated-activation-of-creb-implications-for-multiple-sclerosis
#5
Malabendu Jana, Supurna Ghosh, Kalipada Pahan
An increase in central nervous system (CNS) remyelination and a decrease in CNS inflammation are important steps to halt the progression of multiple sclerosis (MS). RNS60 is a bioactive aqueous solution generated by subjecting normal saline to Taylor-Couette-Poiseuille flow under elevated oxygen pressure. Recently we have demonstrated that RNS60 exhibits anti-inflammatory properties. Here, we describe promyelinating property of RNS60. RNS60, but not normal saline (NS), RNS10.3 (TCP-modified saline without excess oxygen) or PNS60 (saline containing excess oxygen without TCP modification), stimulated the expression of myelin-specific genes and proteins (myelin basic protein, MBP; myelin oligodendrocyte glycoprotein, MOG and proteolipid protein, PLP) in primary mouse oligodendroglia and mixed glial cells...
November 15, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29143151/next-generation-anti-cd20-monoclonal-antibodies-in-autoimmune-disease-treatment
#6
Fanny Huynh Du, Elizabeth A Mills, Yang Mao-Draayer
The clinical success of anti-CD20 monoclonal antibody (mAb)-mediated B cell depletion therapy has contributed to the understanding of B cells as major players in several autoimmune diseases. The first therapeutic anti-CD20 mAb, rituximab, is a murine-human chimera to which many patients develop antibodies and/or experience infusion-related reactions. A second generation of anti-CD20 mAbs has been designed to be more effective, better tolerated, and of lower immunogenicity. These include the humanized versions: ocrelizumab, obinutuzumab, and veltuzumab, and the fully human, ofatumumab...
November 16, 2017: Auto- Immunity Highlights
https://www.readbyqxmd.com/read/29141825/radiculopathy-in-neuromyelitis-optica-how-does-anti-aqp4-ab-involve-pns
#7
Seungyeon Kim, Joonghyun Park, Bum Sun Kwon, Jin-Woo Park, Ho Jun Lee, Jin-Ho Choi, Kiyeun Nam
BACKGROUND: Until recently, the peripheral nervous system (PNS) had been known to be spared in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). However, some studies of late have reported PNS damage in demyelination diseases of the central nervous system (CNS) such as MS and NMOSD. Although multiple studies have reported characteristics reminiscent of peripheral neuropathy in MS, there have been limited reports in NMOSD. To investigate the incidence and pathology of peripheral neuropathy in NMOSD, we reviewed articles describing such cases including our own case...
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29141817/lymphocytes-in-the-treatment-with-interferon-beta-1-b
#8
Zbyšek Pavelek, Oldřich Vyšata, Blanka Klímová, Ctirad Andrýs, Doris Vokurková, Martin Vališ
BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease affecting the central nervous system. One of the basic medications for the treatment of a clinically isolated syndrome (CIS) or relapsing-remitting MS is interferon beta (INFβ). Although the exact mechanism of its effects is unknown, the medication has an anti-inflammatory and immunomodulatory effect. The goal of this study was to determine the characters which are affected in patients treated with INFβ...
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29141574/anti-inflammatory-activity-of-extra-virgin-olive-oil-polyphenols-which-role-in-the-prevention-and-treatment-of-immune-mediated-inflammatory-diseases
#9
Carmela Santangelo, Rosaria Vari, Beatrice Scazzocchio, Patrizia De Sanctis, Claudio Giovannini, Massimo D'Archivio, Roberta Masella
Altered inflammatory response characterizes chronic immune-mediated inflammatory diseases (IMID) such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, and psoriasis. Accumulating evidence indicates that regular consumption of extra virgin olive oil (EVOO), the main source of fat in the Mediterranean diet, is associated with a reduced risk of developing chronic degenerative disorders such cardiovascular diseases, type 2 diabetes and cancer. The beneficial effects on health of EVOO have been attributed, besides to the monounsaturated fats content, to the presence of phenolic compounds that have antioxidant, anti-inflammatory and immunomodulatory properties...
November 13, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29141544/recent-updates-on-the-phytochemistry-pharmacological-and-toxicological-activities-of-zingiber-zerumbet-l-roscoe-ex-sm
#10
Md Areeful Haque, Ibrahim Jantan
BACKGROUND: Zingiber zerumbet (L.) Roscoe ex Sm. (family, Zingiberaceae) is a potent medicinal herb widely known as shampoo ginger and its rhizome is used in numerous ethnomedicinal applications including as antipyretic, anti-inflammatory, antibacterial, anti-diarrheal, antidiabetics, carminative, and diuretic. AIM: The aim of this review was to bring together all of scientific updates on the phytochemistry and pharmacological activities of this herb, including their toxicological studies, and critically analyzed the outcomes to provide directions for future research on the herb as potential source of bioactive metabolites for pharmaceutical and nutraceutical applications...
November 14, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/29141529/experimental-autoimmune-encephalomyelitis-eae-model-of-cynomolgus-macaques-induced-by-recombinant-human-mog1-125-rhmog1-125-protein-and-mog34-56-peptide
#11
Yunxiao Sun, Zhen Peng, Libiao Zhang, Huaqian Wang, Xiangyang He, Xingwen Peng, Qin Zhang, Hui Liu, Junhua Rao, Haifeng Wang, Jie Wu
Experimental autoimmune encephalomyelitis (EAE) induced by self-myelin antigen is a widely used multiple sclerosis (MS) model for preclinical studies of new therapeutics and potential pathogenesis. By comparison with rodent EAE models, EAE models in primates are more similar to MS. Some groups have developed EAE models in primates by using common marmoset (Callithrix jacchus). However, this model has some limitations. EAE in cynomolgus monkey (Macaque fasciculrais) could overcome these limitations. In this study, EAE was induced in cynomolgus monkey by immunizing with the recombinant human myelin oligodendrocyte glycoprotein extracellular domain (1-125) (rhMOG1-125) and a synthetic peptide, representing peptide 34-56 of human myelin oligodendrocyte glycoprotein (MOG34-56) in complete Freund's adjuvant (CFA) and in combination with intravenous injection of pertussis toxin, and subsequent booster immunizations with the same dose of antigen in incomplete Freund's adjuvant (IFA) until the animals developed clinically significant EAE (score≥2)...
November 9, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/29138805/extracellular-polysaccharides-purified-from-aureobasidium-pullulans-sm%C3%A2-2001-polycan-inhibit-dexamethasone%C3%A2-induced-muscle-atrophy-in-mice
#12
Jong-Min Lim, Young Joon Lee, Hyung-Rae Cho, Dong-Chan Park, Go-Woon Jung, Sae Kwang Ku, Jae-Suk Choi
The present study assessed the beneficial skeletal muscle‑preserving effects of extracellular polysaccharides from Aureobasidium pullulans SM‑2001 (Polycan) (EAP) on dexamethasone (DEXA)‑induced catabolic muscle atrophy in mice. To investigate whether EAP prevented catabolic DEXA‑induced muscle atrophy, and to examine its mechanisms of action, EAP (100, 200 and 400 mg/kg) was administered orally, once a day for 24 days. EAP treatment was initiated 2 weeks prior to DEXA treatment (1 mg/kg, once a day for 10 days) in mice...
November 10, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29137549/the-impact-of-a-long-acting-oral-sphingosine-1-phosphate-analogue-on-ovarian-aging-in-a-rat-model
#13
Sezcan Mumusoglu, Volkan Turan, Hasan Uckan, Aysegul Suzer, Lale Karakoc Sokmensuer, Gurkan Bozdag
In animal studies, intravenous continuous infusion or peritoneal injection of sphingosine-1-phosphate (S1P) has been shown to decrease chemotherapy- and radiotherapy-induced apoptosis on primordial follicles. Although a long-acting oral form of an S1P analogue (FTY720, fingolimod) has been recently developed and utilized in women with multiple sclerosis, there are no data exploring its ability to avoid spontaneous follicle apoptosis. Thirty 10-month-old female rats were randomly assigned to 3 groups to investigate whether fingolimod would be able to decrease the spontaneous ovarian follicle apoptosis ratio...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/29137141/steroid-and-xenobiotic-receptor-signalling-in-apoptosis-and-autophagy-of-the-nervous-system
#14
REVIEW
Agnieszka Wnuk, Małgorzata Kajta
Apoptosis and autophagy are involved in neural development and in the response of the nervous system to a variety of insults. Apoptosis is responsible for cell elimination, whereas autophagy can eliminate the cells or keep them alive, even in conditions lacking trophic factors. Therefore, both processes may function synergistically or antagonistically. Steroid and xenobiotic receptors are regulators of apoptosis and autophagy; however, their actions in various pathologies are complex. In general, the estrogen (ER), progesterone (PR), and mineralocorticoid (MR) receptors mediate anti-apoptotic signalling, whereas the androgen (AR) and glucocorticoid (GR) receptors participate in pro-apoptotic pathways...
November 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29129815/biological-effects-of-adipocytes-in-sulfur-mustard-induced-toxicity
#15
Hua Xu, Zhongcai Gao, Peng Wang, Bin Xu, Yajiao Zhang, Long Long, Cheng Zong, Lei Guo, Weijian Jiang, Qinong Ye, Lili Wang, Jianwei Xie
Sulphur mustard (2,2'-dichloroethyl sulfide; SM) is a vesicant chemical warfare agent whose mechanism of acute or chronic action is not known with any certainty and to date there is no effective antidote. SM accumulation in adipose tissue (AT) has been originally verified in our previous study. To evaluate the biological effect caused by the presence of abundant SM in adipocyte and assess the biological role of AT in SM poisoning, in vitro and in vivo experiments were performed. High content analysis revealed multi-cytotoxicity in SM exposed cells in a time and dose dependent manner, and adipocytes showed a relative moderate damage compared with non-adipocytes...
November 9, 2017: Toxicology
https://www.readbyqxmd.com/read/29129090/screening-and-prevention-strategies-and-endoscopic-management-of-early-esophageal-cancer
#16
James A Kim, Pari M Shah
Esophageal cancer is the 8th most common cancer worldwide and the 6th most common cause of cancer-related death. Its two main subtypes, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), have varying incidences globally, but recent decades have seen a demonstrated rise of EAC in Western countries whereas ESCC remains highly prevalent in Eastern Africa, Central Asia, and China. Screening interventions have focused on using endoscopy to identify Barrett's esophagus (BE) as a precursor to EAC, and squamous cell dysplasia prior to onset of ESCC...
October 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29128153/should-we-broaden-indications-for-anti-jcv-antibody-tests-in-multiple-sclerosis-patients-comments-anti-jcv-antibody-index-in-multiple-sclerosis-care
#17
https://www.readbyqxmd.com/read/29127522/common-genetic-variation-within-mir-146a-predicts-disease-onset-and-relapse-in-multiple-sclerosis
#18
Yuan Zhou, Ming Chen, Steve Simpson, Robyn M Lucas, Jac C Charlesworth, Nicholas Blackburn, Ingrid van der Mei, Anne-Louise Ponsonby, Bruce V Taylor
Despite extensive studies focusing on the changes in expression of microRNAs (miRNAs) in multiple sclerosis (MS) compared to healthy controls, few studies have evaluated the association of genetic variants of miRNAs with MS clinical course. We investigated whether a functional polymorphism in the MS associated miR-146a gene predicted clinical course (hazard of conversion to MS and of relapse, and annualized change in disability), using a longitudinal cohort study of persons with a first demyelinating event followed up to their 5-year review...
November 10, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/29127031/sulfur-mustard-induced-mast-cell-degranulation-in-mouse-skin-is-inhibited-by-a-novel-anti-inflammatory-and-anticholinergic-bifunctional-prodrug
#19
Laurie B Joseph, Gabriella M Composto, Roberto M Perez, Hong-Duck Kim, Robert P Casillas, Ned D Heindel, Sherri C Young, Carl J Lacey, Jaya Saxena, Christophe D Guillon, Claire R Croutch, Jeffrey D Laskin, Diane E Heck
Sulfur mustard (SM, bis(2-chloroethyl sulfide) is a potent vesicating agent known to cause skin inflammation, necrosis and blistering. Evidence suggests that inflammatory cells and mediators that they generate are important in the pathogenic responses to SM. In the present studies we investigated the role of mast cells in SM-induced skin injury using a murine vapor cup exposure model. Mast cells, identified by toluidine blue staining, were localized in the dermis, adjacent to dermal appendages and at the dermal/epidermal junction...
November 7, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29126030/evaluating-the-effect-of-adding-fish-oil-to-fingolimod-on-tnf-%C3%AE-il1%C3%AE-il6-and-ifn-%C3%AE-in-patients-with-relapsing-remitting-multiple-sclerosis-a-double-blind-randomized-placebo-controlled-trial
#20
Sasan Zandi-Esfahan, Mehdi Fazeli, Vahid Shaygannejad, Javad Hasheminia, Shervin Badihian, Maryam Aghayerashti, Helia Maghzi
OBJECTIVES: Fish oil is claimed to improve outcome in multiple sclerosis (MS) through anti-inflammatory and antioxidant effects by reducing cytokines including TNF-α, IFN-γ, IL6, and IL-1β. We aimed to evaluate the efficacy of adding fish oil to Fingolimod on these serum cytokines. PATIENTS AND METHODS: This double-blind randomized trial was conducted during April 2015 to September 2016 in Isfahan, Iran. Patients with diagnosis of relapsing remitting MS, aged 18-45years old and expanded disability status scale (EDSS) ≤5 were enrolled in the study...
October 3, 2017: Clinical Neurology and Neurosurgery
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